多功能金属有机骨架材料的构筑及其诊疗一体化应用

Dual-modality imaging and integration of diagnosis-treatment play key roles for the early diagnosis and treatment of some diseases. This project proposes the preparation of multifunctional metal-organic frameworks (MOFs) with porphyrin and tris-bipyridine ruthenium as building blocks, respectively. The MOFs will be used for dual-modility imaging and integration of diagnosis-treatment. Manganese porphyrins show near infrared fluorescence and magnetic resonance (MR) response. Therefore, manganese porphyrin-MOFs will be used for fluorescence and MR dual-modality imaging. Combined with the light-sensitivity property of porphyrins, the integrated application of dual modality imaging and photodynamic therapy will be afforded. To make full use of porous MOFs to load drug, such as doxorubicin, the manganese porphyrin MOFs can be used as diagnosis-treatment platform for dual modality imaging and drug release. Gd-Ru MOFs will be prepared with the carboxylated tris-bipyridine ruthenium and gadolinium ions as the building blocks. Fluorescence and magnetic resonance dual-modality imaging will be achieved with the Gd-Ru MOFs by the use of the red fluorescence of tris-bipyridine ruthenium and magnetic resonance response of gadolinium ions. While the use of metal-organic complexes as building blocks promotes the building of multifunctional MOFs, it also improves the development of MOFs and their applications with multifunctional integration for bioimaging and the integration of diagnosis-treatment.

双模态成像和诊疗一体化对于疾病的早期诊断和快速治疗具有重要意义。本项目提出分别以卟啉和三联吡啶钌为基础制备多功能金属有机骨架材料(MOFs)并将其用作双模态成像及诊疗一体化探针。利用锰卟啉的近红外荧光和磁共振响应实现锰卟啉MOFs的荧光-磁共振双模态成像。结合卟啉的光敏特性发展双模态成像—光敏治疗一体化应用；利用卟啉MOFs的疏水空腔载药实现双模态成像—药物治疗一体化。以钆离子和羧基化三联吡啶钌为构筑单元制备Gd-Ru MOFs，利用三联吡啶钌的红色荧光和钆的磁共振响应实现Gd-Ru MOFs的荧光-磁共振双模态成像。本项目创新性的利用金属有机配合物丰富MOFs的功能，一方面促进多功能MOFs的发展，另一方面为诊疗一体化提供新途径。

金属有机骨架材料(MOFs)是由金属离子和配体形成的多孔材料，开发其功能，拓展其应用具有重要的研究意义和实用价值。我们以三联吡啶钌和卟啉为基础，结合其他可实现成像和治疗的配体或金属离子，利用MOFs孔道装载药物或光热/光动力治疗剂，实现了从多模态成像，到单模态成像-多模式治疗，再到多模态成像-多模式治疗的发展。提出了多发光MOFs的概念，进一步利用MOFs配体和金属节点的多选择性，结合MOFs孔道装载性，发展了多发光MOFs的设计策略，开发了多发光MOFs应用。相关成果发表论文21篇，获授权专利2项。